We have identified and characterized a novel proprietary (US Patent #5,440,022) hepatocyte-derived cytokine originally isolated from human fetal hepatocytes. This molecule is uniquely mitogenic for hepatocytes and hepatocyte cell lines including fetal hepatocytes; hence our designation, hepatopoietin. Highly purified hepatopoietin protects mice from CCl/4-induced liver cell injury. In preliminary studies we obtained a cDNA for hepatopoietin using an expression cloning approach. In phase 1 we will express the cDNA for hepatopoietin and purify sufficient quantities of recombinant protein for biological studies. The activity of the protein will be evaluated using in vitro assays of hepatocyte growth and differentiation and using in vivo assays of hepatocyte growth and regeneration. In phase 2 other preclinical animal models, pharmacology and toxicology studies will be carried out in preparation for submission of an Investigational New Drug Application. Therapy with hepatopoietin may benefit patients with diverse conditions affecting the liver, including not only acute liver injury due to toxins and acute viral hepatitis, but also chronic active hepatitis of diverse origin. PROPOSED COMMERCIAL APPLICATION This novel hepatopoietin will provide a novel therapeutic moiety of various acute and chronic diseases of the liver. This will represent a significant market opportunity.